A Sequential Phase 2b and Phase 3 Study to Evaluate the Efficacy and Safety of AZD4831 in Participants with Heart Failure with Left Ventricular Ejection Fraction > 40%
- Conditions
- Heart Failure with Left Ventricular Ejection Fraction > 40%MedDRA version: 20.0Level: LLTClassification code 10019279Term: Heart failureSystem Organ Class: 100000004849Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2020-005844-47-HU
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 1485
1. = 40 to = 85 years of age, at the time of signing the informed consent.
2. Documented stable symptomatic HF (New York Heart Association Class II-IV) for at least 1 month at Screening (Visit 1), and typical symptoms and signs of HF since at least 1 month (transient HF in the setting of an MI does not qualify) prior to screening (Visit 1). Participants must be receiving a stable dose of an oral diuretic agent for at least 1 month prior to Visit 1 with no more than 50% dose adjustment in the last month.
3. LVEF > 40%, documented by the most recent echocardiogram, or cardiac magnetic resonance imaging within the last 12 months prior to Screening (Visit 1).
4. 6MWD = 30 meters and = 400 meters at Screening (Visit 1) and Randomisation (Visit 3). Difference in 6MWD between Screening and Randomisation must be < 50 meters.
5. KCCQ-TSS = 80 points at Screening (Visit 1) and Randomisation (Visit 3)
6.NT-proBNP = 300 pg/mL (sinus rhythm) or = 600 pg/mL (atrial fibrillation/flutter) at Screening (Visit 1).
7.At least one of the following:
(a) Structural heart disease, ie, LA enlargement and/or left ventricular hypertrophy at the echocardiogram performed at Screening (Visit 1). Left atrial enlargement is defined by at least 1 of the following: LA width (diameter) = 3.8 cm or LA length = 5.0 cm, or LA area = 20 cm2 or LA volume = 55 mL or LAVI > 34 mL/m2. Left ventricular hypertrophy is defined by septal thickness or posterior wall thickness = 1.1 cm or LVMI > 95 g/m2 in women and > 115 g/m2 in men.
(b) Spectral tissue Doppler echocardiography - E/e’ ratio (average of septal and lateral) = 13 at rest at the echocardiogram performed at Screening (Visit 1).
(c) Indirectly estimated elevation of PASP by TRmax velocity > 2.8 m/s (PASP > 35 mmHg) at the echocardiogram performed at Screening (Visit 1) OR directly measured pulmonary capillary wedge pressure > 15 mmHg at rest within the past 12 months or > 25 mmHg at exercise documented by right heart catheterisation within 12 months prior to Screening (Visit 1).
(d) HF decompensation within 6 months before Randomisation (Visit 3), defined as hospitalisation for HF or IV diuretic treatment for HF during an urgent, unscheduled visit without hospitalisation.
8.Body mass index = 18.0 kg/m2 and = 45.0 kg/m2
9.Male or female of non-childbearing potential.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 445
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1040
1 eGFR < 30 mL/min/1.73m2 (Chronic Kidney Disease-Epidemiology Collaboration formula) at Screening (Visit 1).
2. Systolic blood pressure < 90 mmHg or = 160 mmHg if not on treatment with = 3 blood pressure lowering medications or = 180 mmHg irrespective of treatments at Randomisation
3. Heart rate > 110 bpm or < 50 bpm at Randomisation
4. Life expectancy < 3 years due to other reasons than cardiovascular disease.
5. History or ongoing allergy/hypersensitivity reactions to drugs (including but not limited to rash, angioedema, acute urticaria).
6. Presence of any disease or condition rather than HF constituting the main reason for limiting the ability to exercise/reduced exercise capacity. It can be assessed by asking the participant what is the main reason for their limitation. If the answer is letter a”, c”, or d” then the participant should be excluded:
(a)Joint, foot, leg, hip or back pain
(b)Shortness of breath and/or fatigue and/or chest pain
(c)Unsteadiness or dizziness
(d)Lifestyle, weather, or I just don't like to be active
7. Current decompensated HF and/or NT-proBNP > 5000 pg/mL at Screening (Visit 1)
8. Documented history of ejection fraction = 40%.
9. Any planned cardiac procedure (eg, coronary revascularisation, ablation of atrial fibrillation/flutter, and/or valve repair/replacement).
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method